Background: Antibodies are key mediators of protective immunity targeting Plasmodium falciparum merozoite invasion of red blood cells (RBCs). The majority of studies have focused on the role of IgG in immunity and have overlooked the role of IgM, but recent reports have highlighted the potential importance of IgM in protection against malaria.
Methods: The role of merozoite-specific IgM in protection against symptomatic malaria was investigated in a longitudinal cohort of children from Papua New Guinea (PNG). The induction and maintenance of IgM was investigated following naturally acquired malaria and experimentally induced human malaria infection model. IgM fractions were purified from serum samples and the functional activity of IgM in blocking merozoite invasion of RBCs was defined.
Results: Merozoite-specific IgM responses were associated with protection from clinical malaria in PNG children. There was no difference in the induction and decay of merozoite specific IgM compared to IgG up to a year following a malaria episode and IgM was rapidly induced following experimental human malaria infection. IgM blocked merozoite invasion of RBCs in a complement dependent manner, and mediated the deposition of complement factors on the merozoite surface and promoted parasite lysis.
Conclusions: Together, these findings identify merozoite-specific IgM as an important functional, protective and long-lived antibody isotype targeting blood stage malaria, and thus the induction of IgM responses should be considered to improve vaccine design.